Amalgamating Isatin/Indole/Nitroimidazole with 7‐chloroquinolines via azide‐alkyne cycloaddition: Synthesis, anti‐plasmodial, and cytotoxic evaluation

Abstract

The present paper describes the synthesis, anti-plasmodial, and cytotoxic evaluation of 7-chloroquinoline-based conjugates with isatins/indoles/ nitroimidazoles, obtained via Cu-promoted 1,3-dipolar cycloadditions. On contemplating SAR of the synthesized series, the inclusion of indole and nitroimidazole-core improved the antiplasmodial activities while the isatin seemed to have a lesser effect. The conjugate with a nitroimidazole-core and hexyl chain length as a spacer between the two pharmacophores was found to be most potent among the synthesized series and displayed an IC 50 of 0.12 µM and a selectivity index of 1748.

A Mini Review on Isatin, an Anticancer Scaffold with Potential Activities against Neglected Tropical Diseases (NTDs)

“…Among the synthesized series, the hybrids with a shorter alkyl chain length (ethyl/butyl) as spacer displayed better antiplasmodial activities than the ones with longer chain lengths (hexyl/octyl). The most promising hybrid among the synthesized series, 90 , exhibited an IC 50 of 0.33 μM on the tested strain ( Figure 14 ) [ 110 ].…”

Amide Tethered 4-Aminoquinoline-naphthalimide Hybrids: A New Class of Possible Dual Function Antiplasmodials

“…Mechanistic studies showed that the synthesized molecular template could form a complex with free heme and thus inhibit the hemozoin formation. Thus, in an extension to that work and continuing our endeavor for producing antiplasmodial entities, − the present manuscript encompasses the synthesis of 4-aminoquinoline-naphthalimide hybrids connected through amide bond functionality. The compounds were screened for in vitro antiplasmodial potential against both CQ-susceptible 3D7 and CQ-resistant W2 strains of P. falciparum .…”